Phosphonomethoxy nucleotide analogs are a class of well known broad-spectrum anti-viral compounds with the activities against HIV, HBV, CMV, HSV-1, HSV-2 and human Herpes virus as well as other viruses. 9-[2-(phosphonomethoxy) ethyl]adenine (PMEA) and 9-[(R)-2-(phosphonomethoxy)propyl]adenine (PMPA) are two examples of this kind of compounds that have been used in clinical anti-viral treatment. Because of the influence of phosphoric acid moiety in the phosphonomethoxy nucleotide analog on its absorption by human body, phosphonomethoxy nucleotide analog usually needs to be transformed to its lipophilic prodrug to enhance the bioavailability. For example, Adefovir Dipivoxil for hepatitis B treatment and Tenofovir Disoproxil Fumarate for AIDS treatment, which were approved recently by FDA, are lipophilic prodrugs of phosphonomethoxy nucleotide analogs PMEA and PMPA respectively. In vivo, Adefovir Dipivoxil and Tenofovir Disoproxil Fumarate can be metabolized to their corresponding parent compound PMEA and PMPA, which have anti-viral activity.

Nephrotoxicity of Adefovir Dipivoxil was observed in recent clinical trials. Adefovir Dipivoxil will inhibit HIV at the dosage of about 300 mg/day, but the related pharmacokinetic studies showed that a large portion of Adefovir Dipivoxil distributed in kidney when a dosage of 300 mg of Adefovir Dipivoxil was taken into the human body, which caused the nephrotoxicity. When Adefovir Dipivoxil is administered at the dosage of 50 mg/day, 30 mg/day and 10 mg/day respectively, it results in the inhibition of the replication of Hepatitis B virus (HBV) in human body, however, a higher incidence of adverse reaction and renal dysfunction was observed at the dosage of 50 mg/day and 30 mg/day. So Adefovir Dipivoxil can only be administered at a suboptimal dosage of 10 mg/day for the treatment of Hepatitis B. Presently it's also proposed that the cumulative toxicity to kidney needs to be monitored even at the dosage of 10 mg/day when the treatment is beyond 48 weeks.
The dosage of Tenofovir Disoproxil Fumarate approved by FDA for the combination treatment of AIDS and virus infection is 300 mg/day. And this relative high dose will lead to heavy burden to patient's liver and kidney with long-term use of this medicine as well as higher production cost of the unit dosage formulation.
In existing literatures, there is only TD oil reported, which has poor stability and is not suitable for formulation, so it needs to be solidified to facilitate its preparation and storage. Till now, there is no report on the solid TD as well as the preparation thereof.